What are the symptoms of Rocky Mountain Spotted Fever. How is RMSF transmitted. Can Rocky Mountain Spotted Fever be fatal if left untreated. What is the recommended treatment for RMSF. How can you prevent tick bites and reduce your risk of RMSF.

Understanding Rocky Mountain Spotted Fever: A Potentially Life-Threatening Tick-Borne Illness

Rocky Mountain Spotted Fever (RMSF) is a bacterial infection that has gained notoriety as the most serious tick-borne illness in the United States. Caused by the bacterium Rickettsia rickettsii, this disease is transmitted through the bite of an infected tick. Despite its name, RMSF is not limited to the Rocky Mountain region and can occur throughout the country.

The incidence of RMSF has been on the rise over the past decade, with approximately 2,000 cases reported to the Centers for Disease Control and Prevention (CDC) annually. This translates to about six cases per million people per year in the United States. While considered rare, the potential severity of the disease makes it a significant public health concern.

Recognizing the Symptoms: Early Detection is Crucial

RMSF symptoms typically manifest between 2 and 14 days after a tick bite. The sudden onset of symptoms can often be mistaken for other illnesses, making early diagnosis challenging. Key symptoms include:

• High fever (102-103°F) persisting for 2-3 weeks
• Severe headache
• Chills and muscle aches
• Nausea and vomiting
• Abdominal pain
• Fatigue and poor appetite

One of the most distinctive features of RMSF is the development of a rash. This typically appears 2-5 days after the onset of fever, starting on the wrists, palms, ankles, and soles of the feet before spreading inward towards the torso. However, it’s important to note that 10-15% of RMSF patients may not develop a rash at all.

The Progression of the Rash

As the disease progresses, a second, more serious rash may appear around the sixth day of infection. This rash is typically purple-red in color and signifies that the disease has advanced to a more severe stage. Medical professionals aim to initiate treatment before this second rash develops.

The Culprits Behind RMSF: Understanding Tick Vectors

RMSF is transmitted exclusively through tick bites. The primary vectors responsible for spreading the disease include:

1. American dog tick (Dermacentar variablis)
2. Rocky Mountain wood tick (Dermacentor andersoni)
3. Brown dog tick (Rhipicephalus sanguineus)

These tiny arachnids can be as small as a pinhead, making them difficult to detect. The risk of infection increases the longer a tick remains attached to the skin. Interestingly, only about half of RMSF patients recall being bitten by a tick, further complicating diagnosis.

Can RMSF Spread from Person to Person?

RMSF is not contagious and cannot be transmitted directly from person to person. However, pet owners should be aware that dogs can also contract RMSF. While you can’t get the disease directly from your dog, an infected tick on your pet could potentially transfer to you during close contact.

Diagnosing RMSF: Challenges and Considerations

Diagnosing RMSF can be challenging due to its flu-like symptoms and the fact that not all patients develop the characteristic rash. Healthcare providers must rely on a combination of clinical symptoms, potential tick exposure history, and laboratory tests to make an accurate diagnosis.

Blood tests can detect antibodies to R. rickettsii, but these may not be present in the early stages of the disease. As a result, treatment is often initiated based on clinical suspicion before laboratory confirmation is available.

Treatment Protocols: Swift Action is Key

The primary treatment for RMSF is the antibiotic doxycycline, which is effective for both children and adults. In cases of pregnancy, chloramphenicol may be prescribed as an alternative. The CDC strongly recommends initiating treatment as soon as RMSF is suspected, even before laboratory confirmation.

Ideally, treatment should begin within the first five days of symptom onset to prevent serious complications. If treatment is delayed beyond this window, patients may require intravenous antibiotics and hospitalization for monitoring and supportive care.

What Happens if RMSF is Left Untreated?

Untreated or inadequately treated RMSF can lead to severe complications affecting multiple organ systems. These may include:

• Meningitis (inflammation of the brain)
• Inflammation of the heart and lungs
• Kidney failure
• Gangrene in extremities
• Enlargement of the liver or spleen

In the most severe cases, untreated RMSF can be fatal. This underscores the critical importance of early diagnosis and prompt treatment.

Long-Term Effects: Understanding the Potential for Lasting Impact

While many patients recover fully with appropriate treatment, severe cases of RMSF can result in long-term health issues. These may include:

• Neurological deficits
• Hearing loss or deafness
• Muscle weakness
• Partial paralysis

The severity and duration of these long-term effects can vary significantly between individuals. Ongoing medical care and rehabilitation may be necessary for those experiencing lasting complications.

Prevention Strategies: Reducing Your Risk of RMSF

Given the potential severity of RMSF, prevention is paramount. Key strategies for reducing your risk include:

1. Avoiding tick-infested areas when possible
2. Using EPA-approved insect repellents
3. Wearing long-sleeved shirts and long pants when outdoors
4. Conducting thorough tick checks after spending time in potential tick habitats
5. Removing attached ticks promptly and properly
6. Treating pets with tick-prevention products

Proper Tick Removal Technique

If you find a tick attached to your skin, it’s crucial to remove it correctly to minimize the risk of disease transmission. Use fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible. Pull upward with steady, even pressure. After removal, clean the bite area and your hands with rubbing alcohol or soap and water.

The Role of Climate Change in RMSF Prevalence

Climate change is increasingly recognized as a factor influencing the distribution and prevalence of tick-borne diseases like RMSF. Warmer temperatures and changes in precipitation patterns can affect tick populations and their habitats, potentially leading to increased human exposure.

Researchers are studying these ecological shifts to better understand and predict future trends in RMSF occurrence. This information is crucial for public health planning and disease prevention strategies.

Advances in RMSF Research: Looking Towards the Future

Ongoing research into RMSF focuses on several key areas:

• Developing more rapid and accurate diagnostic tests
• Exploring new treatment options and antibiotic alternatives
• Investigating potential vaccine candidates
• Improving tick control methods
• Enhancing public health surveillance and reporting systems

These research efforts aim to reduce the incidence and impact of RMSF, potentially saving lives and preventing long-term health complications.

The Promise of Genomic Research

Advances in genomic sequencing are providing new insights into the R. rickettsii bacterium and its interactions with both ticks and human hosts. This research could lead to novel treatment approaches and more effective prevention strategies in the future.

RMSF in Different Populations: Understanding Varied Risk Factors

While anyone can contract RMSF, certain populations may be at higher risk or experience more severe outcomes. These include:

• Children under 10 years old
• Older adults
• People with compromised immune systems
• Individuals living in or visiting endemic areas
• Outdoor workers and recreational enthusiasts

Understanding these risk factors can help guide targeted prevention efforts and ensure prompt medical attention for those most vulnerable to severe RMSF.

RMSF in Pregnancy

Pregnant women who contract RMSF face additional risks, including potential complications for both mother and fetus. Close medical monitoring and appropriate antibiotic treatment are crucial in these cases. Healthcare providers must carefully balance the risks of the disease against potential medication effects on the developing fetus.

Global Perspective: RMSF Beyond the United States

While RMSF is most commonly associated with the United States, similar tick-borne rickettsial diseases occur in other parts of the world. These include:

• Mediterranean spotted fever in Europe and Africa
• Japanese spotted fever in Asia
• Australian tick typhus

Understanding the global distribution of these related diseases is important for travelers and healthcare providers alike, as symptoms and treatment approaches may be similar to those for RMSF.

International Collaboration in Rickettsial Disease Research

The global nature of tick-borne diseases has led to increased international collaboration among researchers. These efforts aim to share knowledge, improve diagnostic capabilities, and develop more effective prevention and treatment strategies worldwide.

The Economic Impact of RMSF: Beyond Individual Health Concerns

The impact of RMSF extends beyond individual health outcomes, affecting communities and healthcare systems. Factors contributing to the economic burden of RMSF include:

• Direct medical costs for diagnosis and treatment
• Lost productivity due to illness and recovery
• Long-term care costs for patients with lasting complications
• Public health expenditures for surveillance and prevention programs

Understanding these economic implications is crucial for policymakers and health officials when allocating resources for RMSF prevention and control efforts.

The Role of Health Insurance in RMSF Treatment

Access to adequate health insurance can significantly impact RMSF outcomes by ensuring timely diagnosis and treatment. Patients without insurance may delay seeking medical care, increasing the risk of severe complications. Addressing these disparities is an important aspect of comprehensive RMSF management strategies.

Education and Awareness: Key Components in RMSF Prevention

Public education plays a crucial role in preventing RMSF and ensuring early treatment. Key areas of focus for educational initiatives include:

1. Tick identification and habitat awareness
2. Proper use of insect repellents and protective clothing
3. Techniques for thorough tick checks
4. Recognition of early RMSF symptoms
5. Importance of prompt medical attention

Healthcare provider education is equally important, ensuring that medical professionals are equipped to recognize, diagnose, and treat RMSF effectively.

The Role of Community-Based Prevention Programs

Community-led initiatives can be particularly effective in raising awareness and implementing prevention strategies. These may include local tick surveillance programs, community education events, and coordinated efforts to manage tick habitats in public spaces.

Technological Advancements in RMSF Prevention and Management

Emerging technologies are offering new tools in the fight against RMSF and other tick-borne diseases. These include:

• Smartphone apps for tick identification and risk assessment
• GPS-based tick activity forecasting
• Advanced tick control methods, such as targeted pesticide application
• Wearable devices that repel ticks or alert users to their presence

While many of these technologies are still in development or early adoption stages, they represent promising avenues for enhancing RMSF prevention efforts.

The Potential of Artificial Intelligence in RMSF Diagnosis

Artificial intelligence and machine learning algorithms are being explored as tools to improve RMSF diagnosis. These systems could potentially analyze patient symptoms, lab results, and environmental factors to assist healthcare providers in making faster, more accurate diagnoses.

Rocky Mountain Spotted Fever: Pictures and Long-Term Effects

What is Rocky Mountain spotted fever?

Rocky Mountain spotted fever (RMSF) is a bacterial infection spread by a bite from an infected tick. It causes vomiting, a sudden high fever around 102 or 103°F, headache, abdominal pain, rash, and muscle aches.

RMSF is considered the most serious tick-borne illness in the United States. Though the infection can be treated successfully with antibiotics, it can cause serious damage to internal organs, or even death if it isn’t treated right away. You can reduce your risk by avoiding tick bites or promptly removing a tick that has bitten you.

The symptoms of Rocky Mountain spotted fever typically begin between 2 and 14 days after getting a tick bite. Symptoms come on suddenly and usually include:

• high fever, which may persist for 2 to 3 weeks
• chills
• muscle aches
• headache
• nausea
• vomiting
• fatigue
• poor appetite
• abdominal pain

RMSF also causes a rash with small red spots on the wrists, palms, ankles, and soles of the feet. This rash begins 2 to 5 days after the fever and eventually spreads inward towards the torso. After the sixth day of infection, a second rash can develop. It tends to be purple-red, and is a sign that the disease has progressed and become more serious. The goal is to begin treatment before this rash appears.

RMSF can be difficult to diagnose, as the symptoms mimic other illnesses, such as the flu. Although a spotted rash is considered the classic symptom of RMSF, about 10 to 15 percent of people with RMSF don’t develop a rash at all. Only about half of people who develop RMSF remember having a tick bite. This makes diagnosing the infection even more difficult.

RMSF is transmitted, or spread, through the bite of a tick that’s infected with a bacterium known as Rickettsia rickettsii. The bacteria spread through your lymphatic system and multiply in your cells. Though RMSF is caused by bacteria, you can only be infected with the bacteria via a tick bite.

There are many different types of ticks. Types that may be vectors, or carriers, of RMSF include the:

• American dog tick (Dermacentar variablis)
• Rocky Mountain wood tick (Dermacentor andersoni)
• brown dog tick (Rhipicephalus sanguineus)

Ticks are small arachnids that feed on blood. Once a tick has bitten you, it may draw blood slowly over several days. The longer a tick is attached to your skin, the greater the chance of an RMSF infection. Ticks are very small insects — some as small as the head of a pin — so you may never see a tick on your body after it bites you.

RMSF is not contagious and can’t be spread from person to person. However, your household dog is also susceptible to RMSF. While you can’t get RMSF from your dog, if an infected tick is on your dog’s body, the tick can migrate to you while you’re holding your pet.

Learn more about tick bites »

Treatment for Rocky Mountain spotted fever involves an oral antibiotic known as doxycycline. It’s the preferred drug for treating both children and adults. If you’re pregnant, your doctor may prescribe chloramphenicol instead.

The CDC recommends that you start taking the antibiotic as soon as the diagnosis is suspected, even before your doctor receives the laboratory results needed to definitively diagnose you. This is because delay in treating the infection can lead to significant complications. The goal is to begin treatment as soon as possible, ideally within the first five days of infection. Make sure you take the antibiotics exactly the way your doctor or pharmacist described.

If you don’t begin receiving treatment within the first five days, you might require intravenous (IV) antibiotics in the hospital. If your disease is severe or you have complications, you may have to stay in the hospital for a longer period of time to receive fluids and be monitored.

If it isn’t treated right away, RMSF can cause damage to the lining of your blood vessels, tissues, and organs. Complications of RMSF include:

• inflammation of the brain, known as meningitis, leading to seizures and coma
• inflammation of the heart
• inflammation of the lungs
• kidney failure
• gangrene, or dead body tissue, in the fingers and toes
• enlargement of the liver or spleen
• death (if not treated)

People who have a severe case of RMSF may end up with long-term health problems, including:

• neurological deficits
• deafness or hearing loss
• muscle weakness
• partial paralysis of one side of the body

RMSF is rare, but the number of cases per million people, known as incidence, has been increasing over the last 10 years. The current number of cases in the United States is now around six cases per million people per year.

How common is RMSF?

Around 2,000 cases of RMSF are reported to the Centers for Disease Control and Prevention (CDC) each year. People who live close to wooded or grassy areas and people who are in frequent contact with dogs have a higher risk of infection.

Where is RMSF most commonly found?

Rocky Mountain spotted fever got its name because it was first seen in the Rocky Mountains. However, RMSF is more frequently found in the southeastern part of the United States, as well as parts of:

• Canada
• Mexico
• Central America
• South America

In the United States, 5 states see over 60 percent of RMSF infections:

• North Carolina
• Oklahoma
• Arkansas
• Tennessee
• Missouri

What time of year is RMSF most commonly reported?

The infection can occur at any time of the year, but is more common during the warm weather months, when ticks are more active and people tend to spend more time outside. Most cases of RMSF occur during May, June, July, and August.

What is the fatality rate of RMSF?

RMSF can be fatal. However, in the United States overall, less than 1 percent of people infected with RMSF will die from the infection. Most fatalities occur in the very old or very young, and in cases where treatment was delayed. According to the CDC, children under 10 years of age are 5 times more likely to die from RMSF than adults.

You can prevent RMSF by avoiding tick bites or by removing ticks from your body promptly. Take these precautions to prevent a tick bite:

To prevent bites

1. Avoid densely wooded areas.
2. Mow lawns, rake leaves, and trim trees in your yard to make it less attractive to ticks.
3. Tuck your pants into your socks and your shirt into your pants.
4. Wear sneakers or boots (not sandals).
5. Wear light colored clothing so you can easily spot ticks.
6. Apply insect repellant containing DEET. Permethrin is also effective, but should only be used on clothing, not directly on your skin.
7. Check your clothes and body for ticks every three hours.
8. Perform a thorough check of your body for ticks at the end of the day. Ticks prefer warm, moist areas, so be sure to check your armpits, scalp, and groin area.
9. Scrub your body in the shower at night.

Was this helpful?

If you do find a tick attached to your body, don’t panic. Proper removal is important to decrease the likelihood of infection. Follow these steps to remove the tick:

To remove ticks

• Using a pair of tweezers, grasp the tick as close to your body as possible. Do not squeeze or crush the tick during this process.
• Pull the tweezers upward and away from the skin slowly until the tick detaches. This may take a few seconds and the tick will probably resist. Try not to jerk or twist.
• After removing the tick, cleanse the bite area with soap and water and disinfect your tweezers with rubbing alcohol. Make sure to also wash your hands with soap.
• Place the tick in a sealed bag or container. Rubbing alcohol will kill the tick.

Was this helpful?

If you feel ill or develop a rash or a fever after having a tick bite, see your doctor. Rocky Mountain spotted fever and other diseases transmitted by ticks can be dangerous if they’re not treated right away. If possible, take the tick, inside the container or plastic bag, with you to the doctor’s office for testing and identification.

Rocky Mountain Spotted Fever: Pictures and Long-Term Effects

What is Rocky Mountain spotted fever?

Rocky Mountain spotted fever (RMSF) is a bacterial infection spread by a bite from an infected tick. It causes vomiting, a sudden high fever around 102 or 103°F, headache, abdominal pain, rash, and muscle aches.

RMSF is considered the most serious tick-borne illness in the United States. Though the infection can be treated successfully with antibiotics, it can cause serious damage to internal organs, or even death if it isn’t treated right away. You can reduce your risk by avoiding tick bites or promptly removing a tick that has bitten you.

The symptoms of Rocky Mountain spotted fever typically begin between 2 and 14 days after getting a tick bite. Symptoms come on suddenly and usually include:

• high fever, which may persist for 2 to 3 weeks
• chills
• muscle aches
• headache
• nausea
• vomiting
• fatigue
• poor appetite
• abdominal pain

RMSF also causes a rash with small red spots on the wrists, palms, ankles, and soles of the feet. This rash begins 2 to 5 days after the fever and eventually spreads inward towards the torso. After the sixth day of infection, a second rash can develop. It tends to be purple-red, and is a sign that the disease has progressed and become more serious. The goal is to begin treatment before this rash appears.

RMSF can be difficult to diagnose, as the symptoms mimic other illnesses, such as the flu. Although a spotted rash is considered the classic symptom of RMSF, about 10 to 15 percent of people with RMSF don’t develop a rash at all. Only about half of people who develop RMSF remember having a tick bite. This makes diagnosing the infection even more difficult.

RMSF is transmitted, or spread, through the bite of a tick that’s infected with a bacterium known as Rickettsia rickettsii. The bacteria spread through your lymphatic system and multiply in your cells. Though RMSF is caused by bacteria, you can only be infected with the bacteria via a tick bite.

There are many different types of ticks. Types that may be vectors, or carriers, of RMSF include the:

• American dog tick (Dermacentar variablis)
• Rocky Mountain wood tick (Dermacentor andersoni)
• brown dog tick (Rhipicephalus sanguineus)

Ticks are small arachnids that feed on blood. Once a tick has bitten you, it may draw blood slowly over several days. The longer a tick is attached to your skin, the greater the chance of an RMSF infection. Ticks are very small insects — some as small as the head of a pin — so you may never see a tick on your body after it bites you.

RMSF is not contagious and can’t be spread from person to person. However, your household dog is also susceptible to RMSF. While you can’t get RMSF from your dog, if an infected tick is on your dog’s body, the tick can migrate to you while you’re holding your pet.

Learn more about tick bites »

Treatment for Rocky Mountain spotted fever involves an oral antibiotic known as doxycycline. It’s the preferred drug for treating both children and adults. If you’re pregnant, your doctor may prescribe chloramphenicol instead.

The CDC recommends that you start taking the antibiotic as soon as the diagnosis is suspected, even before your doctor receives the laboratory results needed to definitively diagnose you. This is because delay in treating the infection can lead to significant complications. The goal is to begin treatment as soon as possible, ideally within the first five days of infection. Make sure you take the antibiotics exactly the way your doctor or pharmacist described.

If you don’t begin receiving treatment within the first five days, you might require intravenous (IV) antibiotics in the hospital. If your disease is severe or you have complications, you may have to stay in the hospital for a longer period of time to receive fluids and be monitored.

If it isn’t treated right away, RMSF can cause damage to the lining of your blood vessels, tissues, and organs. Complications of RMSF include:

• inflammation of the brain, known as meningitis, leading to seizures and coma
• inflammation of the heart
• inflammation of the lungs
• kidney failure
• gangrene, or dead body tissue, in the fingers and toes
• enlargement of the liver or spleen
• death (if not treated)

People who have a severe case of RMSF may end up with long-term health problems, including:

• neurological deficits
• deafness or hearing loss
• muscle weakness
• partial paralysis of one side of the body

RMSF is rare, but the number of cases per million people, known as incidence, has been increasing over the last 10 years. The current number of cases in the United States is now around six cases per million people per year.

How common is RMSF?

Around 2,000 cases of RMSF are reported to the Centers for Disease Control and Prevention (CDC) each year. People who live close to wooded or grassy areas and people who are in frequent contact with dogs have a higher risk of infection.

Where is RMSF most commonly found?

Rocky Mountain spotted fever got its name because it was first seen in the Rocky Mountains. However, RMSF is more frequently found in the southeastern part of the United States, as well as parts of:

• Canada
• Mexico
• Central America
• South America

In the United States, 5 states see over 60 percent of RMSF infections:

• North Carolina
• Oklahoma
• Arkansas
• Tennessee
• Missouri

What time of year is RMSF most commonly reported?

The infection can occur at any time of the year, but is more common during the warm weather months, when ticks are more active and people tend to spend more time outside. Most cases of RMSF occur during May, June, July, and August.

What is the fatality rate of RMSF?

RMSF can be fatal. However, in the United States overall, less than 1 percent of people infected with RMSF will die from the infection. Most fatalities occur in the very old or very young, and in cases where treatment was delayed. According to the CDC, children under 10 years of age are 5 times more likely to die from RMSF than adults.

You can prevent RMSF by avoiding tick bites or by removing ticks from your body promptly. Take these precautions to prevent a tick bite:

To prevent bites

1. Avoid densely wooded areas.
2. Mow lawns, rake leaves, and trim trees in your yard to make it less attractive to ticks.
3. Tuck your pants into your socks and your shirt into your pants.
4. Wear sneakers or boots (not sandals).
5. Wear light colored clothing so you can easily spot ticks.
6. Apply insect repellant containing DEET. Permethrin is also effective, but should only be used on clothing, not directly on your skin.
7. Check your clothes and body for ticks every three hours.
8. Perform a thorough check of your body for ticks at the end of the day. Ticks prefer warm, moist areas, so be sure to check your armpits, scalp, and groin area.
9. Scrub your body in the shower at night.

Was this helpful?

If you do find a tick attached to your body, don’t panic. Proper removal is important to decrease the likelihood of infection. Follow these steps to remove the tick:

To remove ticks

• Using a pair of tweezers, grasp the tick as close to your body as possible. Do not squeeze or crush the tick during this process.
• Pull the tweezers upward and away from the skin slowly until the tick detaches. This may take a few seconds and the tick will probably resist. Try not to jerk or twist.
• After removing the tick, cleanse the bite area with soap and water and disinfect your tweezers with rubbing alcohol. Make sure to also wash your hands with soap.
• Place the tick in a sealed bag or container. Rubbing alcohol will kill the tick.

Was this helpful?

If you feel ill or develop a rash or a fever after having a tick bite, see your doctor. Rocky Mountain spotted fever and other diseases transmitted by ticks can be dangerous if they’re not treated right away. If possible, take the tick, inside the container or plastic bag, with you to the doctor’s office for testing and identification.

Rocky Mountain spotted fever. What is Rocky Mountain Spotted Fever?

IMPORTANT
The information in this section should not be used for self-diagnosis or self-treatment. In case of pain or other exacerbation of the disease, only the attending physician should prescribe diagnostic tests. For diagnosis and proper treatment, you should contact your doctor.

Rocky Mountain spotted fever is an acute natural focal zoonosis with a predominantly transmissible mechanism of transmission caused by rickettsiae. The clinical picture is characterized by the presence of fever, general intoxication syndrome, profuse maculo-papular rash with a hemorrhagic component, signs of damage to the nervous and cardiovascular systems. Diagnosis is based on the detection of serological markers in the patient’s blood serum. The PCR method is used. Treatment is with antibiotics from the tetracycline group. In parallel, symptomatic therapy is prescribed.

ICD-10

A77.0 Rickettsia rickettsii spotted fever

• Causes
• Pathogenesis
• Classification
• Symptoms of fever
• Complications
• Diagnostics
• Spotted fever treatment
• Prognosis and prevention
• Prices for treatment

General

The disease was first reported in the highlands of the United States in 1899 year. Spotted fever is known by various names: mountain fever, Brazilian typhus, tick-borne rickettsiosis of America. This nosology is common in the USA, Canada, Central and South America. Characterized by seasonality. The peak incidence is recorded in the spring-summer period, which is associated with the high activity of tick-carriers. Susceptibility is universal, but men aged 40-65 and children under 10 living in rural areas are more likely to get sick. This trend can be explained by the choice of profession (foresters, hunters) and active recreation, respectively.

Rocky Mountain spotted fever

Causes

Spotted fever is caused by the Gram-negative bacterium Rickettsia rickettsii. Differs in the expressed polymorphism. In cells, it is found both in the cytoplasm and in the nucleus. The microorganism is sensitive to heat, quickly inactivated at temperatures above 50 ° C and under the influence of disinfectants. Resistant to freezing, long-term storage in the dried state. The reservoir and source of infection are wild rodents, cattle, and dogs. In addition, certain species of ixodid ticks are considered vectors and persistent reservoirs. Man is a random host. Infection occurs by an insect bite or by crushing and rubbing a tick in the area of ​​scratching. In the carrier, rickettsia persist throughout life and are transmitted transovarially.

Pathogenesis

The pathogenesis of Rocky Mountain spotted fever is associated with the affinity of rickettsiae to endothelial cells. The primary focus after a tick bite is not formed. The parasite enters the regional lymph nodes, and then into the systemic circulation. The pathogen is fixed on endothelial cells, penetrates into them and contributes to the development of necrosis. Vessels of small and medium caliber of various localization are predominantly affected. As a result, parietal thrombi are formed, the production of biologically active substances increases with an increase in the degree of intoxication, antibodies to endotheliocytes begin to be produced.

Around the affected vessels, infiltrates are formed, consisting of lymphocytes, macrophages, plasma cells and microscopically resembling granulomas. Destructive or destructive-proliferative vasculitis develops. When the muscular wall of the vessels is involved in the pathological process, panvasculitis is observed. The most common lesions of the vessels of the kidneys, adrenal glands, skin, heart and brain. A characteristic rash is a consequence of pathomorphological changes in skin vessels. When the lumen is obturated by a thrombus, necrosis of the corresponding anatomical regions is formed.

Classification

The course of rickettsiosis can be varied and accompanied by various symptoms. The main triad of the disease includes a severe febrile reaction, headache, and a characteristic rash that appears over a short period of time. Moderate and severe forms of the disease predominate in clinical practice. American scientists proposed the following classification of Rocky Mountain spotted fever:

• Outpatient form. Subfebrile temperature is observed. Insignificant intoxication with moderate feeling of an indisposition, weakness comes to light. Rashes may be atypical, with uncharacteristic localization, or absent altogether.
• Abortive form. There is a sharp rise in temperature to high numbers. The feverish period is about 7 days. A specific rash also persists for about a week, then disappears, giving way to prolonged pigmentation and flaking.
• Typical shape. A typical clinical picture is formed with severe fever lasting about 3 weeks, headaches and muscle pain. Hemorrhagic rash first appears on the extremities, then spreads to the center of the body.
• Lightning form. It is characterized by an extremely severe course with severe intoxication and decompensation of the state. The patient from the first days may fall into a coma. In most cases, it ends with a fatal outcome in 4-5 days.

Symptoms of fever

The incubation period can be up to 2 weeks, averaging 7 days. Sometimes the height of the disease is preceded by a short prodromal period, manifested by malaise, headaches, loss of appetite. Usually the disease begins acutely with a sharp rise in body temperature to 39-41 ° C, pronounced arthralgia, myalgia and headaches. Abdominal pain mimicking acute appendicitis is possible (more often in children). In some patients, edema of the dorsal side of the palms is revealed. Often there is nausea, vomiting, nosebleeds. In some cases, periorbital edema is formed, the injection of conjunctival vessels. When examining the oral cavity, hemorrhagic rashes on the mucous membranes are found. Gradually, the fever acquires a relapsing character with daily temperature fluctuations up to 1.5 ° C. The feverish period lasts 2-3 weeks.

On the 3rd-5th day of illness, a maculopapular rash appears on the skin of patients. Typical primary localization in the area of ​​the ankle joints, wrists and elbows, followed by spread throughout the body. Elements tend to merge. In severe cases, exanthema is found on the palms and soles. From 8-10 days of the course of the pathology, the rash becomes hemorrhagic in nature, which in severe forms leads to the formation of necrosis in the area of ​​the tips of the nose and auricles, soft palate and genitals. Rashes begin to disappear after a decrease in body temperature. In place of the elements, pigmentation and pityriasis peeling remain for a long time.

Somatic symptoms most often include signs of damage to the cardiovascular system and the central nervous system. Possible hypotension, bradycardia, deafness of heart tones. Tachycardia corresponds to an extremely severe course of the disease. Frequent collapses. The involvement of the nervous system is accompanied by delirium, convulsions, paresis and paraplegia, paralysis of the cranial nerves, the appearance of pathological reflexes, impaired consciousness of varying severity, up to the development of coma. Hepatolienal syndrome is rarely detected. More than half of patients develop constipation. There are no specific symptoms of damage to the respiratory and urinary systems.

Complications

The most common complications of Rocky Mountain spotted fever are pneumonia and phlebitis. Perhaps the development of glomerulonephritis, myocarditis with the occurrence of acute heart failure, neuritis, iritis and obliterating endarteritis, the formation of gangrene of characteristic localization. With the defeat of the cranial nerves, the appearance of the corresponding symptoms (usually – violations of the functions of the organs of hearing and vision) is noted. Sometimes convulsions, meningism, Guillain-Barré syndrome are detected. The most formidable complication is coma. On the part of the gastrointestinal tract, bleeding of various localization, perforation, hepatomegaly with jaundice can be observed. There have been cases of rapid decompensation in individuals suffering from alcoholism, and in black men with a deficiency of glucose-6-phosphate dehydrogenase.

Diagnostics

On physical examination, the infectious disease specialist detects a specific rash on the skin, sometimes the presence of hemorrhagic elements on the oral mucosa. Rarely observed primary affect with regional lymphadenitis. With signs of damage to the central nervous system, a consultation with a neurologist is prescribed, which reveals pathological reflexes and symptoms of damage to the cranial nerves. The following laboratory methods are used to diagnose Rocky Mountain spotted fever:

• General laboratory research. In the general blood test, anemia and thrombocytopenia are determined. According to the results of a biochemical blood test, electrolyte imbalances in the form of hyponatremia are possible, sometimes an increase in the levels of bilirubin, hepatic transaminases, urea and creatinine. Cerebrospinal fluid shows leukocytosis with elevated or normal glucose levels.
• Detection of infectious markers. Use the determination of the increase in the titer of specific antibodies in the patient’s blood by ELISA, RIF. A titer of IgM>1:64, IgG>1:128 is considered diagnostically significant. A bioassay is used to isolate the pathogen. PCR diagnostics has been developed. The complement fixation reaction has a high specificity.

Differential diagnosis is made with other spotted fevers, endemic and epidemic typhus, as well as leptospirosis, yersiniosis and secondary syphilis. It is necessary to exclude monocytic ehrlichiosis and human granulocytic anaplasmosis. Sometimes differentiation with hemorrhagic vasculitis and infectious erythema is required. In children, it is important to distinguish rickettsiosis from group A streptococcal pharyngitis, with a rash following an acute period.

Spotted fever treatment

Treatment should be carried out in a hospital under the supervision of an infectious disease specialist with the possibility of transfer to the intensive care unit. Antibacterial agents of the tetracycline series are prescribed, it is possible to use tetracycline and doxycycline. In the treatment of pregnant women, the drug of choice is chloramphenicol. In parallel, symptomatic therapy is carried out (antipyretic, intravenous infusions). Particular attention is paid to the control of electrolyte and water balance. With the development of complications, the treatment plan is adjusted in accordance with the nature of pathological changes.

Prognosis and prevention

The prognosis is doubtful. Mortality, according to various sources, ranges from 5 to 80%. Early detection of the pathological condition and timely administration of antibacterial drugs contributes to a favorable outcome of the disease. Long-term recovery, especially when various body systems are affected, may be accompanied by the formation of persistent disorders. Specific prophylaxis is not carried out. Non-specific measures include the extermination of rodents and ticks, the wearing of special protective clothing, the use of repellents and personal protective equipment. Proper removal of the tick and early initiation of antimicrobial treatment at the onset of the first symptoms of the disease are of great importance.

You can share your medical history, what helped you with the treatment of Rocky Mountain spotted fever.

References

1. Fitzpatrick’s dermatology in clinical practice. Volume 3 / Goldsmith L.A., Kat S.I., Gilcrest B.A. and others – 2018.
2. Tropical diseases. Textbook / ed. Shuvalova E.P. – 2004.
3. Infectious and parasitic diseases of developing countries. / Chebyshev N.V., Pak S.G. – 2008.
4. This article was prepared based on the site materials: https://www.krasotaimedicina.ru/

IMPORTANT
The information in this section should not be used for self-diagnosis or self-treatment. In case of pain or other exacerbation of the disease, only the attending physician should prescribe diagnostic tests. For diagnosis and proper treatment, you should contact your doctor.

Tick-borne rickettsiosis is a close relative of typhus

Vera Rahr, Yana Igolkina, Nina Tikunova, Valentin Vlasov1), 2021

If you are unlucky enough to fall prey to a blood-sucking tick, you are at risk of getting rickettsiosis, one of the many tick-borne infections. The most famous among them are tick-borne encephalitis and borreliosis, while the risk of infection with other pathogens, such as rickettsia, is clearly underestimated. However, these relatives of typhus pathogens are far from harmless, and in terms of occurrence, rickettsiosis ranks second among bacterial tick-borne infections in the Asian part of our country. Fortunately for us, in Russia, in contrast to North America and Europe, deaths in case of infection with rickettsia are rare. Nevertheless, tick-borne rickettsiosis can occur in severe and sometimes atypical forms; they require hospitalization and adequate treatment.

About the authors

Vera Aleksandrovna Rar — Candidate of Biological Sciences, Researcher at the Laboratory of Molecular Microbiology of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk). Author and co-author of 76 scientific papers.

Yana Petrovna Igolkina — Candidate of Biology, Junior Researcher, Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (Novosibirsk). Author and co-author of 20 scientific papers.

Nina Viktorovna Tikunova – Doctor of Biological Sciences, Head. Laboratory of Molecular Microbiology, ICBiFM SB RAS (Novosibirsk). Graduate of NSU (1984).

Valentin Viktorovich Vlasov — Academician of the Russian Academy of Sciences, Doctor of Chemical Sciences, Professor, Scientific Director of the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk), Head of the Department of Molecular Biology and Biotechnology of Novosibirsk State University. Laureate of the State Prize of the Russian Federation (1999). Author and co-author of more than 500 scientific papers and 30 patents.

At the end of the XIX century. among settlers in the foothills of the Rocky Mountains of Montana (USA), a large-scale outbreak of an unknown disease broke out, with high fever, hemorrhagic rash and other severe symptoms – mortality among patients reached 20-30%. In the first decade of the last century, the pathologist and one of the first American infectious disease specialists, Howard Ricketts, established that human infection occurs as a result of suction of blood-sucking ixodid ticks genus Dermacentor . In the blood of patients, he found small bacterium-like microorganisms and experimentally proved on guinea pigs and monkeys that the infection can be transmitted through infected blood.

The disease was named Rocky Mountain spotted fever , although it was later found to occur throughout virtually all of North America and parts of South America. Ricketts himself in 1910 began to study an unknown disease in Mexico, which turned out to be typhus , and found similarities in both the symptoms and pathogens of this disease and tick-borne fever. During the research, the 39-year-old professor contracted typhus and died.

In 1916, the term “rickettsia” was first used by the Brazilian microbiologist and infectious disease specialist Enrique Rocha Lima, the founder of the theory of rickettsia. Over time, this name was assigned to the entire group of similar microorganisms, which includes pathogens of both tick-borne spotted and typhoid fevers carried by lice and fleas.

In Russia, the first cases of tick-borne rickettsiosis were noted in 1934–1936. in the territories of the Krasnoyarsk Territory and the Far East – approximately at the same time when spring outbreaks of tick-borne encephalitis began to be recorded there. It was a time of active development of the eastern regions of the country, so epidemics of unknown diseases attracted special attention.

Later, scientific expeditions were able to accurately determine the nature of the infection and isolate its causative agent, named Dermacentor oxenus sibirica (later Rickettsia sibirica ). The disease itself was named North Asian tick-borne rickettsiosis , or Siberian tick-borne typhus (Loban, 2002).

This disease is tied to certain areas – natural foci . In our country, they are found in Siberia and the Far East, as well as in neighboring countries – Turkmenistan, Armenia, Kazakhstan and Mongolia. At the same time, the role of vertebrates as a reservoir of infection seems to be insignificant. In practice, rickettsiae are very rarely detected in the same rodents, unlike pathogens of other diseases carried by ticks. As for a person, he, as in the case of other tick-borne infections, becomes only an accidental victim as a result of the bite of an infected tick.

Bacterial “relatives” of mitochondria

Rickettsiae are one of the smallest bacteria: their length does not exceed 1–2 μm, which is comparable to the size of large viruses; moreover, they are unable to grow on nutrient media. Which is not surprising: these bacteria are exclusively intracellular parasites and can only multiply in the cells of living organisms.

The propensity of rickettsiae for a comfortable and safe life is in good agreement with the opinion that these bacteria are evolutionarily closest to extinct microorganisms that became the progenitors of the most important intracellular organelles — mitochondria . These structures are busy producing ATP molecules, the universal source of energy for cells. Mitochondria have their own genome, which is transmitted in a series of generations (including in humans) through the maternal line.

Currently, the genus Rickettsia unites more than 40 species, which are divided into several groups and subgroups. Species of rickettsia pathogenic to humans are included in two main groups: typhus (carriers – lice and fleas) and tick-borne spotted fevers (carriers, respectively, ticks). As for the other groups, their danger to humans has yet to be studied.

The genomes of most known rickettsia species, represented by a single ring chromosome, have already been deciphered. Compared to free-living bacteria, they are small, which in principle is typical for intracellular parasites – why a large genome when you already live on everything ready? Because of this, rickettsia rarely undergo genomic rearrangements, since at such a size, any changes can have disastrous consequences.

But even from this small number of rickettsiae genes, a part was borrowed by them from other organisms. For example, the genome of R. felis contains more than one and a half hundred genes that came to them from other bacteria and even higher organisms ( eukaryotes ).

The loss of some regulatory genes can change the pathogenicity of bacteria, and in any direction. For example, the genome of one of the most pathogenic rickettsia is R. prowazekii , the smallest. But rickettsia can also lose the genes that make it sick.

In the genome of some Rickettsia there are also plasmids – free genetic elements that can be inherited relatively independently and even transmitted from one bacterium to another during conjugation of (the bacterial analogue of the sexual process). But little is known about their role in the life of rickettsiae.

Ab ovo

Of the 36 rickettsia species belonging to the tick-borne spotted fever group, only 16 are dangerous to humans. Tick-borne rickettsiosis is transmitted by sucking on an infected tick. Exception – view R. felis which is carried by fleas. In cats, it causes a feverish state, and in humans, it causes symptoms quite typical for rickettsiosis, and neurological disorders are also possible.

In the body of the mite itself, rickettsia can be found almost everywhere, including the salivary glands and ovaries. Therefore, they can not only be preserved in an individual throughout its life, from larva to adult ( adult ), but also, through the egg, be very effectively transmitted to offspring (Rudakov et al., 2016). And this distinguishes rickettsia from other infectious agents, such as tick-borne encephalitis virus or Borrelia.

Due to the transmission of the pathogen between generations, the infestation of some species of ixodid ticks can reach 70-80%! Therefore, it is dangerous for humans to suck both adult ticks and larvae and nymphs. The larvae particularly attack children and can go unnoticed due to their small size, making it difficult to diagnose when infested.

Certain types of rickettsia “gravitate” to “their” types of ticks – knowledge of these features helps to assess the epidemic situation in different territories.

Thus, in the Asian part of the Russian Federation, the most common species in ticks are Candidatus R. tarasevichiae , R. raoultii , R. helvetica , R. sibirica and R. heilongjiangensis (the last two are the most dangerous for a person). At the same time, for example, species R. raoultii and R. sibirica clearly prefer ticks of the genus Dermacentor (Igolkina et al., 2018a; Mediannikov et al., 2006; Shpynov et al., 2006).

The geography of tick habitat also introduces unexpected changes. So, although Candidatus R. tarasevichiae is most often detected in taiga ticks, on Sakhalin more than 60% of these ticks are infected with a completely different rickettsia – R. helvetica . This difference is probably due to the geographical isolation of the island.

Astrakhan, Siberian, Far Eastern

Most rickettsiosis is characterized by the same typical symptoms: high fever and patchy skin rashes, as well as swollen lymph nodes near the bite site. At the site of tick suction, there is often a sore covered with a dark crust and surrounded by a patch of reddened, inflamed skin. There may be muscle and headaches, lethargy, apathy, sleep disturbances, and in rare cases, neurological disorders.

At the same time, rickettsiosis caused by different pathogens may have characteristic features and differ in the severity of the disease. One of the most severe is Rocky Mountain spotted fever: even with timely treatment, mortality reaches 4%. In Europe, Mediterranean spotted fever is widespread with a mortality rate of up to 2.5%.

“Domestic” rickettsiosis, fortunately, have a milder course. Only two types of tick-borne rickettsiosis are officially registered in the Russian Federation: in the European part (mainly Astrakhan region) Astrakhan spotted fever (20 cases per 100 thousand population) (Rudakov, 2016), in the Asian part – the already mentioned Siberian tick-borne typhus. Most cases of the disease beyond the Urals were registered in the Altai Territory, as well as the Altai Republic (up to 130 cases per 100 thousand population).

But although it is believed that in the Asian part of Russia there is only one tick-borne rickettsiosis, which is caused by R. sibirica , it was recently established that in the Khabarovsk Territory the causative agent is most often species R. heilongjiangensis (Mediannikov et al., 2006). The disease even got its name: Far Eastern tick-borne rickettsiosis .

It is possible to distinguish the causative agents of rickettsiosis only with the help of molecular genetic methods. Thus, it was shown that R. sibirica is indeed the main infectious agent in the Novosibirsk region and Altai (Igolkina et al., 2018b; Granitov et al., 2015), but the rest of the territories of Western and Eastern Siberia remain unexplored in this sense. .

Since the lethal outcome of rickettsiosis is not ruled out even in Russia, the disease must be recognized and treated in a timely manner. Diagnosis is now based on characteristic clinical manifestations, and antibiotics of the tetracycline series are used for treatment (for example, doxycycline ). Rickettsia are also sensitive to chloramphenicols ( levomycetin ) (Rudakov, 2016). Those who have been ill develop strong immunity, and to all tick-borne rickettsiosis, regardless of the pathogen. Relapses are not observed.

But not everything is so smooth here either.

Atypical infections

Recently, in different countries, in addition to the well-studied “typical” tick-borne rickettsiosis, there have been cases with atypical symptoms, the causative agents of which were previously considered non-pathogenic (for example, R. raoultii , Candidatus R. tarasevichiae , R .helvetica ).

As for our country, during the DNA analysis of clinical samples of patients with typical and atypical symptoms from the Novosibirsk region and Altai, it turned out that all people bitten by the “Altai” tick were infected with the same pathogen R. sibirica (with one exception).

But Novosibirsk residents were infected with a whole “bunch” of different rickettsiae. Among them were the species R. raoultii , R. aeschlimannii and R. slovaca — such infections were noted on the territory of the Russian Federation for the first time, while the last two pathogens in ticks on the territory of the Novosibirsk region were not previously detected. Most surprising, however, was the fact that rickettsiae from some patients were new genetic variants that could not be attributed to known species (Igolkina et al., 2018b).

The clinical manifestations of rickettsiosis caused by “uncharacteristic” pathogens varied markedly. Thus, patients infected with R. raoultii were significantly more likely to have meningeal symptoms, with the most severe forms of the disease observed in elderly patients, as well as those with immunodeficiency. It is possible that these rickettsiosis are also found in other regions of Russia, but they cannot be identified on the basis of symptoms alone.

The difficulty of making a diagnosis in atypical cases is also evidenced by the fact that Novosibirsk residents infected with R. slovaca and new genetic variants of rickettsiae, symptoms characteristic of rickettsiosis were not observed.

As for Candidatus R. tarasevichiae , cases of rickettsiosis caused by this bacterium are rare, despite its frequent occurrence in ticks; perhaps it can only cause infection in immunocompromised people. At the same time, one case of the disease in a child caused by simultaneous infection with two types of rickettsia was registered in Russia: Candidatus R. tarasevichiae and R. sibirica . The disease resulted in death (Rudakov et al., 2019).

Increasing in number

Thanks to modern molecular genetic methods, researchers identify not only new genovariants and types of rickettsia, but also their presence in uncharacteristic tick species and in new regions.

So, on the territory of the Khabarovsk Territory, pathogenic for humans R. aeschlimannii were first found – previously this species was found only in the south, in the Crimea and Stavropol, moreover, in ticks of a different kind. An even more intriguing find was made in the Khabarovsk Territory. Rickettsia 9 was found there0162 R. canadensis – This strain was first isolated from ticks found in the United States and Canada, followed by a single finding in South Korea. The Siberian sample turned out to be genetically identical to the South Korean one, which indicates the existence of a rare “Asian” genovariant of this rickettsia (Igolkina et al., 2018a).

Some species of rickettsia, despite their wide distribution, remain in the status of a “candidate species”, as in the case of the above Candidatus R. tarasevichiae . They are so named because they have not been cultured in the laboratory and have not been properly characterized (Roult et al., 2005).

And here it is important to prove that such rickettsiae are indeed new species, and not new genovariants of already known ones. Thus, researchers from Novosibirsk have recently managed to characterize two candidate species ( Candidatus R. principis and Candidatus R. rara ) based on 4–5 genes, discovered in the early 2000s. in the Far East, and thus confirm their “species status” (Mediannikov et al., 2006; Igolkina et al., 2018a).

The base of information on the ways of transmission of rickettsia in nature is also being specified. Thus, it was assumed that ticks, which never attack large mammals and humans, may also participate in this process. For example, in some places in Western Siberia, burrowing ixodid ticks I. trianguliceps and I. apronophorus live together with taiga ticks in some places, which feed on small mammals throughout their entire life cycle. At the same time, larvae and nymphs of taiga ticks can feed on the same animals, which opens up the possibility of the exchange of pathogenic species of rickettsiae.

Researchers from Novosibirsk have for the first time identified various types of rickettsia in burrow mites, including candidate ones, including the new Candidatus R. uralica . However, the genovariants of already known species found in different ticks also generally differed, which indicates a rather high specificity of the “burrow tick-rickettsia” association (Igolkina et al., 2015). Based on these data, transmission of rickettsiae from burrowing mites to other blood-sucking parasites is unlikely.

Recently, the idea of ​​the distribution and pathogenicity of rickettsia has begun to change: new species and, accordingly, new tick-borne rickettsiosis are being discovered all over the world. Thus, only two tick-borne rickettsiosis cases are officially registered in Russia, but recently two new ones have been “unofficially” added to them, and this is probably not the end.

Unlike tick-borne encephalitis and tick-borne borreliosis, rickettsiosis does not become chronic and does not cause severe long-term health effects. However, they all require treatment, and when the disease occurs with unexpressed or uncharacteristic symptoms, it is difficult to make a correct diagnosis. Such atypical cases are often associated with Rickettsia species not previously considered pathogenic.

It is possible to accurately diagnose the disease in complex cases only with the help of molecular genetic or immunological methods, however, as a rule, they are not used in the clinical practice of our country. Moreover, in the Russian Federation today there are simply no domestic licensed test systems for detecting rickettsia antibodies in patient sera.

Rickettsiae are quite widespread: there is evidence that in “risk zones” almost every fifth tick is infected – hence the high incidence of people living in epidemiological foci. In particular, one of the foci of tick-borne rickettsiosis is such a popular holiday destination for Russians as Gorny Altai, where the highest incidence of rickettsiosis in the population is noted. Therefore, in order to improve the accuracy of assessing the epidemic situation and preventing the incidence of these tick-borne infections, it is necessary to continue to study the distribution and species diversity both in clinical samples and in nature.

Literature
1. Loban K. M., Lobzin Yu. V., Lukin E. P. Human rickettsiosis: A guide for physicians. M.; St. Petersburg: ELBI, 2002. 473 p.
2. Rudakov N. V. Rickettsia and rickettsiosis: A guide for physicians. Omsk: Om. scientific vestn., 2016. 424 p.
3. Granitov V., Shpynov S., Beshlebova O., et al. New evidence on tick-borne rickettsioses in the Altai region of Russia using primary lesions, serum and blood clots of molecular and serological study // Microbes Infect. 2015. V. 17(11–12). P. 862–865.
4. Igolkina Y. P., Rar V. A., Yakimen-ko V. V., et al. Genetic variability of Rickettsia spp. in Ixodes persulcatus / Ixodes trianguliceps sympatric areas from Western Siberia, Russia: Identification of a new Candidatus Rickettsia species // Infect. Genet. Evol. 2015. V. 34. P. 88–93.
5. Igolkina Y., Rar V., Vysochina N., et al. Genetic variability of Rickettsia spp.